CN117482146A

CN117482146A - Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating acute lung injury or acute respiratory distress syndrome

Info

Publication number: CN117482146A
Application number: CN202210877911.7A
Authority: CN
Inventors: 张贵民; 李红华; 周继栋
Original assignee: Shandong New Time Pharmaceutical Co Ltd
Current assignee: Shandong New Time Pharmaceutical Co Ltd
Priority date: 2022-07-25
Filing date: 2022-07-25
Publication date: 2024-02-02

Abstract

The invention provides an application of a traditional Chinese medicine composition in preparing a medicine for preventing or treating acute lung injury or acute respiratory distress syndrome, and belongs to the technical field of medicines. The Chinese medicinal composition comprises fructus Xanthii, flos Magnoliae, herba Ephedrae, radix Angelicae Dahuricae, herba Menthae, rhizoma Ligustici, scutellariae radix, fructus forsythiae, flos Chrysanthemi Indici, trichosanthis radix, rehmanniae radix, saviae Miltiorrhizae radix, poria, and Glycyrrhrizae radix. The traditional Chinese medicine composition can obviously reduce the lung index of mice with acute lung injury or acute respiratory distress syndrome, lighten the pulmonary alveolar hemorrhage and pulmonary edema degree, lighten the lung injury, has definite curative effect and obvious effect, and is equivalent to dexamethasone sodium phosphate. The traditional Chinese medicine composition has small side effect and high clinical safety, and can be used for a long time.

Description

Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating acute lung injury or acute respiratory distress syndrome

Technical Field

The invention belongs to the technical field of medicines, and relates to application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating acute lung injury or acute respiratory distress syndrome.

Background

Acute lung injury (acute lung injury, ALI) refers to a disease characterized by diffuse dysfunction of the lung caused by a variety of direct or indirect factors such as trauma, infection, inhalation of noxious gases, shock, etc. The clinical manifestations are refractory hypoxia, pulmonary alveoli and pulmonary highly oedema and progressively aggravated respiratory distress, further developing acute respiratory distress syndrome (acute respiratory distress syndrome, ARDS), further developing multiple organ failure with mortality up to 30% -50%, seriously threatening the life health of people. Even if the patient survives, the lung function is seriously impaired, and the quality of life is also seriously affected, causing great mental burden and economic burden to the patient, the family and the society.

The pathogenesis of acute lung injury and acute respiratory distress syndrome is complex, and the pathological process mainly comprises 3 stages: (1) during exudation, pulmonary capillary endothelial cells and type I alveolar epithelial cells are damaged, protein-rich edema liquid and inflammatory cell infiltration exist in pulmonary interstitial and alveolar spaces, inflammatory factors in the lungs are excessively released, and the pro-inflammatory anti-inflammatory system and the oxidation/oxidation resisting system are unbalanced, so that inflammatory cascade reaction like a waterfall is induced, the pulmonary injury is aggravated, microvascular permeability is increased, pulmonary alveoli generate edema and hemorrhage, pulmonary dysfunction and ventilation blood flow proportion imbalance; (2) during the proliferation phase, the type II alveolar epithelial cells start to proliferate and differentiate, and at the same time, the lung interstitial fibroblasts proliferate; (3) during the fibrosis phase, fibroblasts secrete epithelial growth factors and collagen, which when too much collagen is deposited, leads to fibrosis.

The ALI treatment has no specific drug at present, and the conventional treatment method mainly comprises mechanical ventilation therapy, drug therapy, stem cell therapy and gene therapy. The medicines used in the treatment are mainly glucocorticoids, anti-inflammatory medicines, anti-oxidative stress medicines, vasodilators and the like clinically, and can improve damaged lung tissues by improving oxygenation, anti-inflammation, anti-oxidation, endothelial cell function, pulmonary fibrosis, organism immunity regulation and other ways, so that great progress is made, and meanwhile, the medicines also have great adverse reactions, such as glucocorticoids, which are one of the important modes for treating acute lung injury at present, and a great deal of glucocorticoids are mainly used for impact therapy, and the curative effect is related to the receptor level, the functional state and the etiology of the acute lung injury, so that the treatment effect is controversial. A large number of clinical researches prove that the glucocorticoid has poor treatment effect, has the problem of treating the symptoms and the root causes, has large side effects after long-term massive use, and cannot treat ALI fundamentally.

Disclosure of Invention

The first aim of the invention is to provide a traditional Chinese medicine composition for solving the technical problems in the prior art and providing the application of the traditional Chinese medicine composition in preparing medicines for preventing or treating acute lung injury.

The second object of the invention is to provide the application of the traditional Chinese medicine composition in preparing medicines for preventing or treating acute respiratory distress syndrome.

Further, the application of the traditional Chinese medicine composition in preparing medicines for reducing the lung index of acute lung injury or acute respiratory distress syndrome is provided.

The invention provides a traditional Chinese medicine composition, which is prepared from the following raw materials:

preferably, the traditional Chinese medicine composition is prepared from the following raw materials:

further preferably, the traditional Chinese medicine composition is prepared from the following raw materials:

further, the fructus Xanthii in the traditional Chinese medicine composition is fried fructus Xanthii.

Furthermore, the traditional Chinese medicine composition can be prepared into clinically acceptable dosage forms directly through a conventional process or after pharmaceutically acceptable auxiliary materials are added.

Further, the clinically acceptable dosage forms are granules, oral liquid, pills, tablets, syrups and capsules.

Preferably, the clinically acceptable dosage form is a granule.

Furthermore, the human dosage of the traditional Chinese medicine composition is 0.1g/kg/d-20g/kg/d.

Preferably, the human dosage of the traditional Chinese medicine composition is 0.2g/kg/d-10g/kg/d.

The granule for promoting the restoration of the nasal cavity is prepared by adding flavor according to Song Daiyan on the basis of the 'Xanthium sibiricum powder' carried in Jisheng Fang. Is prepared from 14 Chinese-medicinal materials including siberian cocklour fruit, magnolia flower, ephedra, dahurian angelica root, peppermint, ligusticum sinense, baikal skullcap root, capsule of weeping forsythiae capsule, wild chrysanthemum flower, trichosanthes root, rehmannia root, root of red rooted saliva, poria cocos wolf, licorice root. Fructus Xanthii and flos Magnoliae are used as the monarch. Fructus Xanthii has effects of dispelling pathogenic wind, inducing resuscitation, removing dampness, and relieving pain; flos Magnoliae dispelling wind, relieving exterior syndrome, ventilating lung and inducing resuscitation; the two medicines are combined together, so that the effects of dispelling exogenous evils, freeing nasal orifices, eliminating dampness and relieving pain can be achieved. The ephedra is used for dispersing lung qi to assist the resuscitation; radix angelicae is capable of dispelling cold and relieving exterior syndrome, and dispelling wind and relieving pain; herba Menthae is effective in clearing away heat and promoting the circulation of qi, and is helpful for dispelling pathogenic wind and relieving fever; the three medicines are used as ministerial medicines for assisting monarch medicines in dispersing lung qi and dispelling exogenous evils. The scutellaria baicalensis, the fructus forsythiae and the wild chrysanthemum have the effects of clearing heat and detoxicating, so that pathogenic wind-heat can be relieved from the exterior; the ligusticum has the functions of eliminating dampness and dispelling wind, and treating headache; radix Trichosanthis and radix rehmanniae have effects of nourishing yin, moistening dryness, cooling blood, and promoting salivation, so as to make the dryness of Xin Wenyao in the recipe; poria cocos has effects of invigorating spleen and excreting dampness; the red sage root has the effects of promoting blood circulation and removing blood stasis; the above herbs are combined together to strengthen the effect of inducing resuscitation and expelling pus. Licorice root, radix Glycyrrhizae coordinates the other drugs as guiding drugs. Most of the above drugs enter the lung meridian, and the lung opens into the nose. The whole formula is strict in compatibility, reasonable in formula, capable of dispelling exterior cold and clearing interior heat, dispelling exterior cold to induce resuscitation and promote nasal function, and clearing interior heat to permeate brain and stop sneeze. The medicines are combined, and the symptoms and root causes are treated together, so that the effects of dispelling wind, clearing heat, freeing lung and dredging orifices are achieved.

Compared with the prior art, the invention has the beneficial effects that:

1. the traditional Chinese medicine composition can obviously reduce the lung index of mice with acute lung injury or acute respiratory distress syndrome, lighten the pulmonary alveolar hemorrhage and pulmonary edema degree, lighten the lung injury, has definite curative effect and obvious effect, and is equivalent to dexamethasone sodium phosphate.

2. The traditional Chinese medicine composition has small side effect and high clinical safety, and can be used for a long time.

Drawings

Fig. 1 lung tissue pathological section of mice in each group of acute lung injury or acute respiratory distress syndrome model, magnification: 40.0X.

A: normal group; b: a model group; c: a positive drug group; d: low dose group;

e: medium dose group; f: high dose group.

Having an embodiment of

The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Example 1 preparation of granules

Among them, the one stir-baked Xanthium sibiricum is preferable.

Adding 450ml of the above 14 medicines into flos Magnoliae, herba Menthae, rhizoma Ligustici and flos Chrysanthemi Indici to extract volatile oil, and collecting distilled water solution and residue respectively; decocting the rest materials in 2100ml water for 3 hr, filtering, mixing the residues with the above residue, decocting in 2100ml water for 1.5 hr for 3 times, filtering, mixing all the filtrates with the above distilled water solution of flos Magnoliae, and concentrating to obtain fluid extract; mixing with adjuvants, granulating, spraying volatile oil, and sealing for 24 hr to obtain granule.

Example 2 preparation of granules

Among them, the one stir-baked Xanthium sibiricum is preferable.

Adding 750ml of volatile oil into the four medicines of flos Magnoliae, herba Menthae, rhizoma Ligustici and flos Chrysanthemi Indici, extracting, and collecting distilled water solution and residue respectively; decocting the rest materials in 5500ml water for 3 hr, filtering, mixing the residues with the residues, decocting in 5500ml water for 1.5 hr for 3 times, filtering, mixing all the filtrates with the distilled water solution of flos Magnoliae, and concentrating to obtain fluid extract; mixing with adjuvants, granulating, spraying volatile oil, and sealing for 24 hr to obtain granule.

Example 3 preparation of granules

Among them, the one stir-baked Xanthium sibiricum is preferable.

Adding 75ml of the above 14 medicines into flos Magnoliae, herba Menthae, rhizoma Ligustici and flos Chrysanthemi Indici to extract volatile oil, and collecting distilled water solution and residue respectively; decocting the rest materials in 705ml water for 1 hr, filtering, mixing the residues with the residues, decocting in 705ml water for 0.5 hr for 1 time, filtering, mixing all the filtrates with the distilled water solution of flos Magnoliae, etc., and concentrating to obtain fluid extract; mixing with adjuvants, granulating, spraying volatile oil, and sealing for 24 hr to obtain granule.

Example 4 preparation of pills

Among them, the one stir-baked Xanthium sibiricum is preferable.

Adding 300ml of the above 14 medicines into flos Magnoliae, herba Menthae, rhizoma Ligustici and flos Chrysanthemi Indici to extract volatile oil, and collecting distilled water solution and residue respectively; decocting the rest materials in 1500ml water for 2 hr, filtering, mixing the residues with the above residue, decocting in 1500ml water for 1 hr for 2 times, filtering, mixing all the filtrates with the above distilled water solution of flos Magnoliae, etc., and concentrating to obtain fluid extract; finally adding pharmaceutically acceptable auxiliary materials through conventional procedures to prepare pills.

Example 5 preparation of tablets

Among them, the one stir-baked Xanthium sibiricum is preferable.

550ml of the volatile oil is extracted from the four medicines of magnolia flower, peppermint, ligusticum, wild chrysanthemum, and the distilled aqueous solution and the dregs are respectively collected by another device; decocting the rest materials with 2500ml water for 2 hr, filtering, mixing the residues with the above residue, decocting with 2500ml water for 1 hr for 2 times, filtering, mixing all the filtrates with the above distilled water solution of flos Magnoliae, etc., and concentrating to obtain fluid extract; finally adding pharmaceutically acceptable auxiliary materials through conventional procedures to prepare tablets.

Example 6 preparation of capsules

Among them, the one stir-baked Xanthium sibiricum is preferable.

Adding 900ml of the above 14 medicines into flos Magnoliae, herba Menthae, rhizoma Ligustici and flos Chrysanthemi Indici to extract volatile oil, and collecting distilled water solution and residue respectively; decocting the rest materials with 2500ml water for 2 hr, filtering, mixing the residues with the above residue, decocting with 2500ml water for 1.5 hr for 2 times, filtering, mixing all the filtrates with the above distilled water solution of flos Magnoliae, and concentrating to obtain fluid extract; finally adding pharmaceutically acceptable auxiliary materials through conventional procedures to prepare capsules.

Example 7 preparation of oral liquid

Among them, the one stir-baked Xanthium sibiricum is preferable.

Adding 100ml of the above 14 medicines into flos Magnoliae, herba Menthae, rhizoma Ligustici and flos Chrysanthemi Indici to extract volatile oil, and collecting distilled water solution and residue respectively; decocting the rest materials in 1800ml water for 2 hr, filtering, mixing the residues with the above residue, decocting in 1800ml water for 1 hr for 2 times, filtering, mixing all the filtrates with the above distilled water solution of flos Magnoliae, etc., and concentrating to obtain fluid extract; finally adding pharmaceutically acceptable auxiliary materials through conventional procedures to prepare the oral liquid.

Example 8 Effect of nasal Brillouin orifice-opening particles on acute Lung injury or acute respiratory distress syndrome in mice caused by tracheal instillation of lipopolysaccharide

1. Experimental materials

1.1 experimental animals: SPF grade ICR mice, 3 weeks old, weighing 20-22g, male, 90.

1.2 experimental drugs:

nasosinusitis-relieving granule: shandong New era pharmaceutical Co., ltd., lot number: 0022010017

Positive drug: dexamethasone sodium phosphate injection, chenxin pharmaceutical Co., ltd., batch number: 2108230612

Shutai 50: french Vickers Co., ltd., lot number: 7XDYA

Injection of hydrochloric acid and chlorphenamine maleate: jilin province Hua Murray animal health products effective company, lot number: 2020118

2. Experimental method

2.1 grouping and administration

After 7d of adaptive feeding before the experiment, the feed is randomly divided into 6 groups, and 15 groups are respectively a normal group, a model group, a low-dose group, a medium-dose group, a high-dose group and a positive drug group of the nasosinusitis-relieving particles. The administration doses of the low dose group, the medium dose group and the high dose group are respectively 2.93g/kg, 5.86g/kg and 11.72g/kg of nasosinusitis particles (which are equivalent to 1/2, 1 and 2 times of clinical doses), the administration mode is gastric lavage administration, the administration volume is 10ml/kg, the positive pharmaceutical group is 5mg/kg of dexamethasone sodium phosphate injection by intraperitoneal injection, the normal group and the model group are gastric lavage administration of equal volumes of purified water, and the administration is carried out for 13 days continuously for 1 time per day.

2.2 moulding

Molding after the administration of each group on day 12. Firstly, after the abdominal anesthesia by using Shutai 50, fixing the mice on an operation plate, disinfecting the neck, longitudinally cutting the skin of the neck, peeling subcutaneous tissues, exposing the trachea, instilling purified water to the trachea of the normal group of mice by using a microsyringe, instilling 0.1ml of lipopolysaccharide solution (1.7 mg/ml) to the trachea of each group of mice, and establishing a model of acute lung injury or acute respiratory distress syndrome of the mice. After 24h molding, the mice were sacrificed for material.

2.3 observations index

2.3.1 pulmonary index

Lung index = lung weight (mg)/body weight (g), which can be used to assess the severity of pulmonary edema. The results are shown in Table 1.

2.3.2 Lung wet weight/Dry weight (W/D)

Pulmonary dry/wet ratio= (pulmonary dry weight wet/pulmonary wet weight dry ratio) can be used to assess the severity of pulmonary edema. The results are shown in Table 1.

2.3.3 Lung tissue treatment

Mouse lung tissue was fixed in formalin solution for pathological observation. The results are shown in FIG. 1.

2.3.4 statistical methods

Statistical treatment with SPSS17.0 software, experimental data in "mean.+ -. Standard deviation"In the form of (c) the comparison between groups uses one-way analysis of variance and the comparison between the two groups uses t-test. With P<0.05 indicates that the difference is statistically significant.

3. Experimental results

3.1 influence of the particles for inducing resuscitation in nasosinusitis on lung index and lung wet weight/dry weight (W/D)

TABLE 1 influence of Biyuan Tongqiao particles on lung index and Lung wet weight/Dry weight (W/D)

Note that: comparison with Normal group p<0.01; comparison with model group ^# p<0.05， ^## p<0.01。

As can be seen from Table 1, the model group had significantly increased lung index and W/D compared to the normal group, and had extremely significant statistical difference (p < 0.01), and the modeling was successful. Compared with the model group, the lung index and W/D of the high-dose group are significantly reduced, and the statistical difference is found (p < 0.05); the lung index of the positive drug group has no statistical difference (p > 0.05), the W/D is obviously reduced, and the lung index of the positive drug group has statistical difference (p < 0.01). The results show that the nasosinusitis orifice-opening particles can obviously reduce the lung index and W/D, relieve the pulmonary edema degree, relieve the lung injury, and have definite curative effect, which is equivalent to dexamethasone sodium phosphate.

3.2 pathological influence of the particles for inducing resuscitation in nasosinusitis on pulmonary tissue

As can be seen from FIG. 1, compared with the normal group, acute lung injury of mice caused by lipopolysaccharide, alveolar hemorrhage and pulmonary edema of pulmonary tissue of mice in the model group, alveolar hemorrhage and pulmonary edema of each administration group are improved to different degrees, and the medium-high dose group is equivalent to the positive drug group. The nasosinusitis-inducing particles can relieve the damage degree of lung tissues, have the effect of treating lung injury, and have remarkable effect, and are equivalent to dexamethasone sodium phosphate.

The inventors have studied the effect of the nasal sinuses orifice-opening particles and the granules of the embodiment 2 on acute lung injury or acute respiratory distress syndrome of mice caused by instilling lipopolysaccharide into the trachea according to the experimental method of the embodiment 8, and the results show that the improvement effect of the nasal sinuses orifice-opening particles and the granules of the embodiment 2 on a disease model is equivalent to that of dexamethasone sodium phosphate. In addition, the granule group for nasosinusitis opening is superior to the granule group of example 2 in terms of index improvement, and has a significant difference in lung index compared with the granule group of example 2.

The nasosinusitis-inducing particles are a pure traditional Chinese medicine preparation, and since the nasosinusitis-inducing particles are approved and marketed, adverse reactions are only occasional diarrhea, symptoms disappear after general drug withdrawal, side effects are small, and the nasosinusitis-inducing particles have good clinical safety.

Dexamethasone sodium phosphate is an adrenocortical hormone medicine, and has great side effects after long-term massive use. Mo Jiangwei et al (research progress of side effects of traditional Chinese medicine for treating glucocorticoid: henan traditional Chinese medicine: 2016.36 (5): 914-917) disclose that glucocorticoid has various side effects during application, such as hypercortisolism (manifestations of cushing's syndrome such as central obesity, full moon face, buffalo back, acne, hirsutism, etc.), metabolic disorder (hormonal blood sugar, blood pressure elevation, water, electrolyte disorder, etc.), induction or aggravation of infection, ulcer, psychosis, inhibition of growth and development of children, etc.

Compared with dexamethasone sodium phosphate, the granule has small side effect and good clinical safety, and can be used for a long time.

Claims

1. Application of a Chinese medicinal composition in preparing medicine for preventing or treating acute lung injury is provided.

2. Application of a Chinese medicinal composition in preparing medicine for preventing or treating acute respiratory distress syndrome is provided.

3. The use according to any one of claims 1-2, wherein the use of the traditional Chinese medicine composition in the manufacture of a medicament for reducing the lung index of acute lung injury or acute respiratory distress syndrome.

4. The use according to any one of claims 1 to 3, wherein the Chinese medicinal composition is prepared from the following raw materials:

5. the use according to claim 4, wherein the Chinese medicinal composition is prepared from the following raw materials:

6. the use according to claim 5, wherein the Chinese medicinal composition is prepared from the following raw materials:

7. the use according to any one of claims 4-6, wherein the fructus Xanthii in the herbal composition is a fried fructus Xanthii.

8. The use according to any one of claims 1 to 7, wherein the Chinese medicinal composition is formulated into a clinically acceptable dosage form by conventional techniques either directly or after addition of pharmaceutically acceptable excipients.

9. The use according to claim 8, wherein the clinically acceptable dosage form is a granule, an oral liquid, a mixture, a pill, a tablet, a syrup, a capsule.

10. The use according to claim 9, wherein the clinically acceptable dosage form is a granule.